Sortilin (SEQ ID NO:1) sometimes also referred to as Neurotensin receptor 3 (NTR3), Glycoprotein 95 (Gp95) or 100 kDa NT receptor of Swiss Prot ID No. Q99523 is the archetypical member of a mammalian family of neuronal receptors (1-3) defined by the unique Vps10p-domain (Vps10p-D) that among other ligands binds neurotrophic factors and neuropeptides (4-8). This domain constitutes the entire luminal part of Sortilin (sSortilin) and is activated for ligand binding by enzymatic propeptide cleavage (4, 5). Sortilin is a multifunctional type-1 receptor capable of endocytosis as well as intracellular sorting (9-11), and as shown recently, it also engages in signaling by triggering proneurotrophin-induction of p75NTR-mediated neuronal apoptosis (6, 7, 12, 13). Sortilin is synthesized as a proprotein, which is converted to mature Sortilin by enzymatic cleavage and removal of a short N-terminal propeptide. Only the mature receptor binds ligands and interestingly, all its known ligands, e.g. Neurotensin (NT; SEQ ID NO:10), lipoprotein lipase, the proforms of nerve growth factor-β (proNGF) and brain derived neurotrophic factor (proBDNF), receptor associated protein (RAP), and its own propeptide, compete for binding (5-7, 10), indicating that the diverse ligands target a shared or partially shared binding site. NT is a tridecapeptide, which binds to Sortilin, SorLA (another Vps10p-D receptor) and the two G-protein coupled receptors NTR1 and NTR2 (4, 14-16). The physiological role of NT in relation to Sortilin has not been fully elucidated (17), still NT is an important tool, as it inhibits all other ligands from binding to the Sortilin Vps10p-D.